2,2'-[1,4-Phenylenebis(oxymethylene)]diquinoline | 187879-48-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2,2'-[1,4-Phenylenebis(oxymethylene)]diquinoline
• 英文别名: 2-[[4-(quinolin-2-ylmethoxy)phenoxy]methyl]quinoline
• CAS: 187879-48-7
• 化学式: C₂₆H₂₀N₂O₂
• 分子量: 392.457
• InChiKey: AFZFCCFVKBTBTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-甲基喹啉 在 sodium carbonate decahydrate 、 sodium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 6.25h， 生成 4-(2-喹啉基甲氧基)苯酚 、 2,2'-[1,4-Phenylenebis(oxymethylene)]diquinoline
  参考文献：
  名称：

  The Process Development of RG 12525 (2-{[4-(Tetrazol-5-ylmethylphenyl)-methoxy]phenoxymethyl}quinoline)

  摘要：

  This contribution describes process improvements to provide a practical and cost effective synthesis for the manufacture of RG 12525 which resulted in a 3-fold increase in overall yield. Improved solvent systems for chlorination and azidation reactions are described. Adjustments to the tetrazole-forming step eliminated azide sublimation and minimised this risk on scaleup. A robust solvent system was found to control the polymorphic form during crystallisation, which had hitherto been difficult due to the near-equivalence of melting points (154 and 157 degreesC) of the two known forms.

  DOI：

  10.1021/op0000677

文献信息

• A convergent synthesis of an LTD4 antagonist, RG12525
  作者：Adam W. Sledeski、Michael K. O'Brien、Larry K. Truesdale

  DOI：10.1016/s0040-4039(96)02460-4

  日期：1997.2

  An efficient, convergent synthesis of an LTD4 antagonist, RG12525 (1) has been achieved through the alkylation of the (2-quinolinylmethoxy)phenol (2) with either a triphenylmethyl protected tetrazole synthon (4a) or with a tetrahydropyranyl derivative (4b). Preparation of synthons 4a and 4b, as well as novel preparation of 2 is described.

  LTD 4拮抗剂RG12525（1）的高效，聚合反应已通过将（2-喹啉基甲氧基）苯酚（2）与三苯甲基保护的四唑合成子（4a）或与四氢吡喃基衍生物（4b）烷基化来实现。描述了合成子4a和4b的制备以及2的新制备。
• Approaches to p-hydroxyphenoxymethylquinolines which avoid intermediate chloromethylquinolines for the synthesis of the LTD4 antagonist, RG 12525
  作者：M.K. O'Brien、A.W. Sledeski、L.K. Truesdale

  DOI：10.1016/s0040-4039(96)02361-1

  日期：1997.1

  As part of an effort to develop an industrial synthesis of the LTD(4) antagonist RG 12525 (1), several approaches to the intermediate (2-quinolinylmethoxy)phenol 3 were investigated that avoided the generation of the lachrymatory sensitizer alpha-chloro-2-methylquinoline 2. Utilization of a cyclic sulfate in place of alpha,alpha'-dichloro-o-xylene 4 showed promise as a selective dialkylating agent in the conversion of 3 to RG 12525 (1). (C) 1997, Elsevier Science Ltd. All rights reserved.
• The Process Development of RG 12525 (2-{[4-(Tetrazol-5-ylmethylphenyl)-methoxy]phenoxymethyl}quinoline)
  作者：Andrew W. Bridge、Ronald H. Jones、Humayun Kabir、Alex A. Kee、David J. Lythgoe、Mustafa Nakach、Clive Pemberton、John A. Wrightman

  DOI：10.1021/op0000677

  日期：2001.1.1

  This contribution describes process improvements to provide a practical and cost effective synthesis for the manufacture of RG 12525 which resulted in a 3-fold increase in overall yield. Improved solvent systems for chlorination and azidation reactions are described. Adjustments to the tetrazole-forming step eliminated azide sublimation and minimised this risk on scaleup. A robust solvent system was found to control the polymorphic form during crystallisation, which had hitherto been difficult due to the near-equivalence of melting points (154 and 157 degreesC) of the two known forms.